Immune Checkpoint Inhibitors in the Treatment of Lymphomas

Lepik, Kirill V.; str., Saint Petersburg L’va Tolstogo

doi:10.21320/2500-2139-2018-11-4-303-312

Cited by 11 publications

(7 citation statements)

References 97 publications

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“…Complete or partial recovery of tumor immune control results in significant attenuation of disease progression. Amplification of 9p24.1 and subsequent overexpression of PD-L1 seems to be the characteristic feature of HL-specific Reed-Sternberg cells [14]. It explains high efficiency of ICIs in cHL.…”

Section: Clinical Studiesmentioning

confidence: 97%

Nivolumab in pediatric Hodgkin's lymphoma

Kozlov¹,

Kazantzev²,

Iukhta³

et al. 2019

CTT

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Immune checkpoint inhibitors (ICIs) are rather efficient in classical Hodgkin's lymphoma (cHL). Pembrolizumab (pembro) is approved in children and demonstrates high response rates with acceptable toxicity. The role of nivolumab (nivo) in pediatric cHL is only to be elucidated. The aim of the presented study was to assess safety and efficiency of nivo in this age group with relapsed or refractory (R-R) cHL. Twenty-one pediatric heavily pre-treated patients 9-18 years old received nivo-based therapy. Overall response was registered in 86% (complete response-57% and partial response-29%). Three-year overall survival (OS) and progression free survival (PFS) were 95% and 29%, respectively. Only 1 clinically significant adverse effect (AE) of nivo was registered in the study (autoimmune thyroiditis). We did not observe any unacceptable toxicity of nivo.

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Section: Clinical Studiesmentioning

confidence: 97%

Nivolumab in pediatric Hodgkin's lymphoma

Kozlov¹,

Kazantzev²,

Iukhta³

et al. 2019

CTT

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Section: Chl Pathogenesis and Neoplastic Pathologymentioning

confidence: 99%

“…24 Such changes lead to increased expression of PDL1, PDL2, and JAK2. 25 More than 87% of patients demonstrate deregulation of the JAK-STAT pathway. Activating mutations in the JAK1 , STAT3 , STAT5B , and STAT6 genes, which are frequently accompanied by inactivating mutations in the SOCS1 gene, can directly contribute to this.…”

Section: Chl Pathogenesis and Neoplastic Pathologymentioning

confidence: 99%

“…In clinical studies, monoclonal anti-PD1 antibodies (nivolumab, pembrolizumab) have been able to achieve an overall response and complete remission in patients with r/r cHL in approximately 70% and 30% of patients, respectively. 25 In >90% of patients with cHL, HRS cells have reduced expression of MHCI 33 and approximately 40% show decreased expression of MHCII, which leads to defective immune surveillance by CD8 and CD4 T cells, respectively. 34 MHCI reduced expression is in most cases due to mutations in the B2M gene.…”

Section: Chl Pathogenesis and Neoplastic Pathologymentioning

confidence: 99%

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CAR-T Cell Therapy for Classical Hodgkin Lymphoma

Katsin,

Dormeshkin,

Meleshko

et al. 2023

HemaSphere

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Classical Hodgkin lymphoma (cHL) is a malignancy characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells within a complex tumor microenvironment (TME). Despite advances in conventional therapies, a subset of cHL patients experience relapse or refractory disease, necessitating the exploration of novel treatment strategies. Chimeric antigen receptor T cell (CAR-T cell) therapy has emerged as a promising approach for the management of cHL, harnessing the power of genetically modified T cells to recognize and eliminate tumor cells. In this article, we provide an overview of the pathogenesis of cHL, highlighting the key molecular and cellular mechanisms involved. Additionally, we discuss the rationale for the development of CAR-T cell therapy in cHL, focusing on the identification of suitable targets on HRS cells (such as CD30, CD123, LMP1, and LMP2A), clonotypic lymphoma initiating B cells (CD19, CD20), and cells within the TME (CD123, CD19, CD20) for CAR-T cell design. Furthermore, we explore various strategies employed to enhance the efficacy and safety of CAR-T cell therapies in the treatment of cHL. Finally, we present an overview of the results obtained from clinical trials evaluating the efficacy of CAR-T cell therapies in cHL, highlighting their potential as a promising therapeutic option. Collectively, this article provides a comprehensive review of the current understanding of cHL pathogenesis and the rationale for CAR-T cell therapy development, offering insights into the future directions of this rapidly evolving field.

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“…ИКТИ значительно улучшили результаты лечения в онкологии [28]. Представители данной группы, а именно ингибиторы программируемой клеточной гибели (PD-1) ниволумаб и пембролизумаб, находят применение в онкогематологии в терапии лимфом [29].…”

Section: результатыunclassified

Approaches to early diagnosis and prevention of cardiovascular toxicity induced by targeted drugs and immune checkpoint inhibitors in oncohematology: a literature review

Мещерина

Степченко

Leontieva

et al. 2023

Cardiovasc Ther Prev

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The development of targeted drugs and immune checkpoint inhibitors (ICIs), as well as their implementation into clinical practice has allowed increasing the overall and event-free survival of oncohematological patients. Currently, assessment of the efficacy of a therapeutic strategy in each specific case includes the evaluation of an acceptable tolerability profile. The subject of discussion includes cardiovascular complications induced by target drugs and ICIs. The review mainly presents the issues of cardiovascular toxicity (CVT) in certain groups of oncohematological patients (with chronic lymphocytic leukemia, chronic myeloid leukemia, multiple myeloma). The spectrum of cardiovascular adverse effects associated with targeted and ICI therapy in oncohematological practice is quite wide — coronary artery disease, peripheral arterial disease, myocarditis, heart failure, arrhythmias, hypertension. The high importance of the problem of using targeted and immunosuppressive therapy dictates the need to predict adverse effects. The diagnosis of heart failure (one of CVT manifestations) is based on determining the decreased left ventricular ejection fraction during echocardiography, less often — during cardiac magnetic resonance imaging; global longitudinal myocardial strain is a significant parameter of preclinical heart failure, which is determined using the speckle tracking technique. To determine vascular toxicity, a special attention is paid to the vascular wall structure and microcirculation parameters — capillary density at rest, percentage of capillary recovery and perfused capillaries, stiffness index for large blood vessels, reflection index for small arteries, laboratory markers of inflammation and endothelial dysfunction (C-reactive protein, fibrinogen, homocysteine, endothelin 1, vascular endothelial growth factor). CVT prevention presumes the determination of the risk group, correction of risk factors, and administration of protective therapy to very high and high-risk patients. One of the promising directions for preventing vascular toxicity is the use of sodium-glucose linked transporter-2 inhibitors.

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Immune Checkpoint Inhibitors in the Treatment of Lymphomas

Cited by 11 publications

References 97 publications

Nivolumab in pediatric Hodgkin's lymphoma

Nivolumab in pediatric Hodgkin's lymphoma

CAR-T Cell Therapy for Classical Hodgkin Lymphoma

Approaches to early diagnosis and prevention of cardiovascular toxicity induced by targeted drugs and immune checkpoint inhibitors in oncohematology: a literature review

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